Promoter analysis of influenza virus RNA polymerase.

Influenza virus polymerase, which was prepared depleted of viral RNA, was used to copy small RNA templates prepared from plasmid-encoded sequences. Template constructions containing only the 3' end of genomic RNA were shown to be efficiently copied, indicating that the promoter lay solely within the 15-nucleotide 3' terminus. Sequences not specific for the influenza virus termini were not copied, and, surprisingly, RNAs containing termini identical to those from plus-sense cRNA were copied at low levels. The specificity for recognition of the virus sense promoter was further defined by site-specific mutagenesis. It was also found that increased levels of viral protein were required in order to catalyze both the cap endonuclease-primed and primer-free RNA synthesis from these model templates, as well as from genomic-length RNAs. This finding indicates that the reconstituted system has catalytic properties very similar to those of native viral ribonucleoprotein complexes.     

Effect of d-Penicillamine on Poliovirus Replication In HeLa Cells

A series of mercaptan compounds were studied with respect to their ability to inhibit the growth of poliovirus in cultured cells. Of the compounds tested only d-penicillamine possessed antiviral activity. There was no direct effect on the virus itself, nor were the processes of adsorption, penetration and uncoating, or virus-induced "shut-off" of host cell protein synthesis inhibited. At concentrations where there was no effect on host cell RNA or protein synthesis, d-penicillamine caused a marked inhibition of virus-specific RNA and protein synthesis. Although much reduced, the relative concentrations of single-stranded and double-stranded viral RNA synthesized in the presence of d-penicillamine was unchanged. Similarly, all apparent precursor and cleavage product proteins could be synthesized in the presence of the drug. The inhibitory effect was reversible, after a lag of 1.5 to 2 h after removal of the drug, and normal yields of virus could be obtained. The structural and functional properties of d-penicillamine are discussed in relation to requirements for anti-polioviral activity.     

Targeted-nanoliposomal combretastatin A4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment

A number of antiangiogenic drugs have been approved by the Food and Drug Administration which are used in cancer therapy, and variety of other agents in several stages of clinical development or in preclinical assessment. Among these, combretastatin A4 (CA-4) is an under-researched inhibitor of angiogenesis that shows potential activity in the treatment of advanced tumors with migration capacity. However, its clinical application has been limited due to poor water solubility, low bioavailability, rapid metabolism, and systemic elimination. During the last decade, numerous investigations have been done to overcome these problems by using different CA-4 delivery systems or developing produgs of CA-4 or its structural analogs. Nevertheless, these strategies could not be efficient out of the undesired side effects on normal tissues. Nanoliposomal CA-4 not only benefits from the advantage of using liposomal drugs as opposed to free drugs but also can accumulate in the tumor site via specific targeting ligands, which leads to efficient targeting and enhancement of bioavailability. To the best of our knowledge, we consider an important attempt to understand different factors that might influence the CA-4 loading and release pattern of liposomes and the consequent results in tumor therapy. In this review, we shed light on various studied liposomal CA-4 formulations showing application thereof in cancer treatment.     

Gene Regulatory Elements Extraction in Breast Cancer by Hi-C Data Using a Meta-Heuristic Method

Russian Journal of Genetics - Detection of gene regulatory elements and the interactions among them may be conducive to diagnosis and treatment of many diseases and maladies as cancer. In this...